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To explore the therapeutic effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer and the mechanism involved. In vitro cell test: the cytotoxicity of metformin under different oxygen and glucose contents was evaluated using cell survival curves. In vivo xenograft tumor test: NSCLC-A549 cells were injected into mice, which were then divided into the following five groups: control group, metformin group, single high-dose radiotherapy group, metformin 1 h before radiotherapy group, and metformin 24 h after radiotherapy group. Growth of the tumor was evaluated in each group, and the blood flow and histology of the tumor tissues were analyzed. According to the in vitro test results, metformin was the most cytotoxic under hypoxic and low-glucose conditions. The in vivo results showed that the tumor volume was the smallest in the mouse groups administered metformin 1 h before high-dose radiotherapy and 24 h after radiotherapy ((0.47±0.12) cm3 and (0.49±0.21) cm3, respectively). Blood flow analysis showed that single high-dose radiotherapy destroyed the micro-vessels of tumor tissue and reduced the perfusion of oxygen and glucose. Histological analysis revealed that cells in hypoxic and hypoglycemic area of the tumor tissue center were preferentially killed by metformin, whereas there were viable cells in the surrounding well perfused areas. Metformin combined with single high-dose radiotherapy enhanced the toxicity by changing tumor cell metabolism. These results provide theoretical and data support for the future use of metformin combined with stereotactic body radiotherapy.

Since solar cycle 16, the heliospheric current sheet (HCS) has been found to be shifted southward during the late declining to minimum phase. However, this trend is broken at the end of solar cycle 24. In this paper, we analyse the shift of the HCS by using information obtained from coronal model and in situ data provided by the near-Earth OMNI data base and the Parker Solar Probe (PSP). Coronal potential field source surface modelling results show that the northward shift is established at the beginning of 2018 and remains stable for about 2 yr. Interplanetary magnetic field data obtained from and within 1 au also support the northward shift, as the southern polarity T appears more frequently than the northern polarity A between 2018 and 2020. Both model results and in situ observation obtained by PSP imply that the HCS shift is established in the corona, and then propagates into the heliosphere. The quadrupole term still has a significant influence on the formation of the HCS shift. [ABSTRACT FROM AUTHOR]

For a three-dimensional magnetohydrodynamics solar wind model, it is necessary to carry out assessment studies to reveal its ability and limitation. In this paper, the ambient solar wind results of year 2008 generated by the CESE-HLLD 3D MHD model are compared with multipoint in-situ measurements during the late declining phase of solar cycle 23. The near-ecliptic results are assessed both quantitatively and qualitatively by comparing with in-situ data obtained at the L1 point and by the twin STEREO spacecraft. The assessment reveals the model’s ability in reproducing the time series and statistical characteristics of solar wind parameters, and in catching the change of interplanetary magnetic field polarity and the occurrence of the stream interaction regions. We find that the two-stream structure observed near the ecliptic plane is reproduced, but the differences among observations at L1 and the twin STEREO spacecraft are not caught by the model. The latitudinal variation of the results is assessed by comparing with the Ulysses observation. The characters of variation in different latitudinal ranges are duplicated by the model, but biases of the results are seen, and the boundary layers between fast and slow solar wind are sometimes thicker than observation.

Using stochastic resonance (SR) mechanism, the output signal can be enhanced by adding noise to the nonlinear system. Therefore, an image denoising algorithm based on adaptive bi-dimensional stochastic resonance (ABSR) is proposed in this paper. Firstly, the image is sampled as a bi-dimensional signal, and an adaptive bi-dimensional dynamic nonlinear system model is constructed. The peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) of the output image are used as the double evaluation model of the adaptive system, and the optimal parameters of the model are automatically obtained by adjusting the parameters of the dynamic nonlinear system using the reverse positioning method. Compared with the traditional mean filter, median filter and one-dimensional stochastic resonance, the image restoration effect of dynamic adaptive bi-dimensional stochastic resonance is more closer to the original image, and the histogram, PSNR and SSIM of the output image are also significantly better than the other three methods. The results show that dynamic adaptive bi-dimensional stochastic resonance has better denoising effect and better robustness to the change of noise intensity in image processing. [ABSTRACT FROM AUTHOR]

The vehicle longitudinal control algorithm is the core function of the adaptive cruise control system, whose main task is to convert vehicle acceleration and deceleration requirements into vehicle driving and braking commands so that the vehicle can quickly and accurately track the desired acceleration. Traditional longitudinal control algorithms rely on accurate vehicle dynamic modeling or complex controller parameter calibrations. To overcome those difficulties, a longitudinal control algorithm based on RBF-PID is proposed in this paper. The algorithm uses the RBFNN (radial basis function neural network), which can simply and quickly approximate any complex nonlinear system, to identify the Jacobian information of the vehicle and perform parameter tuning for PID control and achieve vehicle longitudinal control with self-tuning capability. Finally, the algorithm of this paper is verified by the joint simulation of Matlab/Simulink and Carsim. The results show that this algorithm has a better response rate and anti-jamming capability than the traditional PID control and can achieve accurate and rapid tracking of the desired acceleration. [ABSTRACT FROM AUTHOR]

Background. Many studies have found that chromatin regulators (CRs) are correlated with tumorigenesis and disease prognosis. Here, we attempted to build a new CR-related gene model to predict breast cancer (BC) survival status. Methods. First, the CR-related differentially expressed genes (DEGs) were screened in normal and tumor breast tissues, and the potential mechanism of CR-related DEGs was determined by function analysis. Based on the prognostic DEGs, the Cox regression model was applied to build a signature for BC. Then, survival and receiver operating characteristic (ROC) curves were performed to validate the signature's efficacy and identify its independent prognostic value. The CIBERSORT and tumor immune dysfunction and exclusion (TIDE) algorithms were used to assess the immune cells infiltration and immunotherapy efficacy for this signature, respectively. Additionally, a novel nomogram was also built for clinical decisions. Results. We identified 98 CR-related DEGs in breast tissues and constructed a novel 6 CR-related gene signature (ARID5A, ASCL1, IKZF3, KDM4B, PRDM11, and TFF1) to predict the outcome of BC patients. The prognostic value of this CR-related gene signature was validated with outstanding predictive performance. The TIDE analysis revealed that the high-risk group patients had a better response to immune checkpoint blockade (ICB) therapy. Conclusion. A new CR-related gene signature was built, and this signature could provide the independent predictive capability of prognosis and immunotherapy efficacy for BC patients. [ABSTRACT FROM AUTHOR]

This paper presents a study of a 2021 October 9 coronal mass ejection (CME) with multipoint imaging and in situ observations. We also simulate this CME from the Sun to Earth with a passive tracer to tag the CME's motion. The coronagraphic images show that the CME is observed as a full halo by SOHO and as a partial halo by STEREO-A. The heliospheric images reveal that the propagation speed of the CME approaches about 1° hr−1, suggesting a slow CME. With simulated results matching these observation results, the simulation discloses that as the CME ejects from the Sun out to interplanetary space, its global morphology is distorted from an ellipsoid to a concave shape owing to interactions with the bimodal solar wind. The cross section of the CME's flux rope structure transforms from a circular shape into a flat one. As a result of the deflection, the propagation direction of the CME is far away from the Sun–Earth line. This means that the CME flank (or the ICME leg) likely arrives at both Solar Orbiter and the L1 point. From the CME's eruption to 1 au, its volume and mass increase by about two orders and one order of magnitude, respectively. Its kinetic energy is about 100 times larger than its magnetic energy at 1 au. These results have important implications for our understanding of CMEs' morphology, as well as their space weather impacts. [ABSTRACT FROM AUTHOR]

Background: Mammography-based breast cancer screening has been widely implemented in many developed countries. Evidence was needed on participation and diagnostic performance of population-based breast cancer screening using ultrasound in China. Methods: We used data from the Cancer Screening Program in Urban China in Beijing from 2014 to 2019 and was followed up until July 2020 by matching with the Beijing Cancer Registry database. Eligible women between the ages of 45 and 69 years were recruited from six districts and assessed their risk of breast cancer through an established risk scoring system. Women evaluated to be at high risk of breast cancer were invited to undergo both ultrasound and mammography. Participation rates were calculated, and their associated factors were explored. In addition, the performance of five different breast cancer screening modalities was evaluated in this study. Results: A total of 49,161 eligible women were recruited in this study. Among them, 15,550 women were assessed as high risk for breast cancer, and 7,500 women underwent ultrasound and/or mammography as recommended, with a participation rate of 48.2%. The sensitivity of mammography alone, ultrasound alone, combined of ultrasound and mammography, ultrasound for primary screening followed by mammography for triage, and mammography for preliminary screening followed by ultrasound for triage were19.2%, 38.5%, 50.0%, 46.2%, and 19.2%, and the specificity were 96.1%, 98.6%, 94.7%, 97.6%, 95.7%, respectively. The sensitivity of combined ultrasound and mammography, ultrasound for primary screening followed by mammography for triage, was significantly higher than mammography alone (p=0.008 and p=0.039). Additionally, ultrasound alone (48,323 RMB ($7,550)) and ultrasound for primary screening followed by mammography for triage (55,927 RMB ($8,739)) were the most cost-effective methods for breast cancer screening than other modalities. Conclusions: Ultrasound alone and ultrasound for primary screening and mammography are superior to mammography for breast cancer screening in high-risk Chinese women. [ABSTRACT FROM AUTHOR]

A global, three-dimensional (3D) numerical simulation model has been employed to study the 3D morphology and kinematics of the large shock driven by the 2017 September 10 coronal mass ejection (CME). Based on actual solar observations, which include the photospheric magnetic field and the CME's speed and source location, the simulation result is delicately tuned by matching with coronal polarized brightness observations and in situ solar-wind measurements at 1 au. The simulation reproduces well the shock's shape and position in coronagraphic images. The shock's physical parameters at 1 au are similar to those constrained from the observations, with the simulated transit time being nearly the same as the observed one. The simulation reveals that the shock around the backward direction keeps propagating away from the Sun, and despite its large extent, the shock cannot be seen as a spherical structure forming a 360° envelope around the Sun. Identified as a fast forward shock, the shock has a sharp velocity jump and a large density compression with a Mach number larger than one from the nose toward the lateral parts, consistent with a driven shock all across the front. Compared to the nose, the right flank of the shock has a weak compression ratio, but probably yields enhanced energetic particles for observers aligned with it. It follows that large CME-driven shocks have the potential to accelerate energetic particles over a wide longitudinal separation and are likely responsible for the production of these particles in the inner heliosphere. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the classification of microscopic tumours using full digital mammography images. Firstly, to address the shortcomings of traditional image segmentation methods, two different deep learning methods are designed to achieve the segmentation of uterine fibroids. The deep lab model is used to optimize the lesion edge detailed information by using the void convolution algorithm and fully connected CRF, and the two semantic segmentation networks are compared to obtain the best results. The Mask RCNN case segmentation model is used to effectively extract features through the ResNet structure, combined with the RPN network to achieve effective use and fusion of features, and continuously optimize the network training to achieve a fine segmentation of the lesion area, and demonstrate the accuracy and feasibility of the two models in medical image segmentation. Histopathology was used to obtain ER, PR, HER scores, and Ki-67 percentage values for all patients. The Kaplan-Meier method was used for survival estimation, the Log-rank test was used for single-factor analysis, and Cox proportional risk regression was used for multifactor analysis. The prognostic value of each factor was calculated, as well as the factors affecting progression-free survival. This study was done to compare the imaging characteristics and diagnostic value of mammography and colour Doppler ultrasonography in nonspecific mastitis, improve the understanding of the imaging characteristics of nonspecific mastitis in these two examinations, improve the accuracy of the diagnosis of this type of disease, improve the ability of distinguishing it from breast cancer, and reduce the rate of misdiagnosis. [ABSTRACT FROM AUTHOR]

Aimed to be ready for the transition from research to operation, we have developed a solar wind model by coupling a data-driven empirical coronal model with a magnetohydrodynamics heliospheric model. We performed a data-driven simulation of the solar wind for a two-year period during the declining and minimum phases of solar cycle 23. Comparisons with OMNI and Ulysses spacecraft data show that the model can reproduce the large-scale variations of the solar wind plasma parameters. The evolution of geocentric solar magnetospheric (GSM) Bx and Bz components are also reasonably duplicated by the model in terms of polarity and strength. Apparent signatures of the Russell–McPherron (R-M) effect are found from both observed data and simulated results, indicating that during the investigated interval the R-M effect is the dominant mechanism that controls the large-scale evolution of the north–south component of the interplanetary magnetic field in the GSM frame. The results demonstrate that the established model can provide valuable space weather information about the solar wind. [ABSTRACT FROM AUTHOR]

The aim of this study was to study the role of Th1/Th2 cell‐associated chemokines in the formation of hypertrophic scars in rabbit ears. Twenty‐six New Zealand white rabbits were used to establish the hypertrophic scar model of rabbit ear and the normal scar model of rabbit's back. Two rabbits were sacrificed on days 0 and 21, 28, 35, 42, 49, 56, and 63 after operation. The specimens were stained with haematoxylin‐eosin (HE). Scar elevation index (SEI) was used to detect the expression of 10 chemokines related to Th1/Th2 cells in both scar formation expressions. Real‐time polymerase chain reaction (PCR) results showed that two chemokines (CXCL10, CXCL12) were highly expressed during the formation of normal scar, and there was almost no expression during the formation of hypertrophic scar (*P < 0.05). The chemokines (CCL2, CCL3, CCL4, CCL5, CCL7, CCL13, CX3CL1) were almost non‐expressed in the formation of normal scars but were expressed for a long time in the formation of hypertrophic scars. The four chemokines, CCL2, CCL4, CCL5, and CX3CL1, maintained a long‐term high expression level during the formation of hypertrophic scars (P < 0.01). There were also three chemokines (CCL14, CCL19, CCL21) that were almost undetectable in normal scarring, but there was transiently low‐level expression (P < 0.05) only during the peak proliferative phase in proliferative scarring. Th1/Th2 cell‐associated chemokines are different in the type, quantity and expression, and maintenance time of rabbit ear hypertrophic scars. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to assess right ventricular (RV) diastolic dysfunction in patients with obstructive sleep apnea syndrome (OSAS) using velocity vector imaging (VVI) and to evaluate the application of VVI technology. Methods: According to the apnea–hypopnea index (AHI), 69 patients with OSAS were divided into three groups: mild, moderate, and severe. A total of 35 cases of healthy subjects were enrolled as the control group. Digital images of apex four‐chamber views were acquired to measure the peak early diastolic strain rate (RV‐SRe), late diastolic strain rate(RV‐SRa), and RV‐SRe/RV‐SRa using VVI. Results: RV‐SRe, RV‐Sra, and RV‐SRe/RV‐SRa were decreasing along with the disease severity. RV‐SRe, RV‐SRe/RV‐SRa in moderate and severe OSAS group showed lower than control and mild OSAS groups. RV‐SRa in severe OSAS group showed lower than control group. RV‐SRe had the best correlation with AHI than other parameters. Conclusions: Right ventricular diastolic dysfunction starts before the development of heart failure and pulmonary hypertension in patients with OSAS. RV‐SRe was the parameter that may reflect subclinical myocardial dysfunction and can better reflect RV diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Immunological factors play important roles in the occurrence of hypertrophic scars. Imiquimod can be used as an immunosuppressive agent to regulate the function of T‐helper (Th) cell subsets Th1 and Th2. In this article, we explored the impact of imiquimod on scar hyperplasia through Th cells. A rabbit ear hypertrophic scar model was built. Four round wounds were cut in each rabbit's ears ventrally with a diameter of 1 cm and bilateral symmetry. All the right ear wounds were treated with 5% imiquimod cream. The blank control group contained all the left ear wounds, which were treated with Vaseline ointment at the same time. Haematoxylin and eosin and Masson staining showed that imiquimod collagen deposition was significantly reduced compared with the control group, scar index (SEI) showed that the proliferative degree reached its peak on the 28th day after operation in blank group, and the degree of hyperplasia was significantly higher than that of the imiquimod group (P < .05). Real‐time Polymerase chain reaction results showed that the imiquimod induced the expression of Th2 cell‐related chemokines CCL2, CCL3, CCL5, CCL7, and CCL13 at each time point, which were significantly lower than that of the blank control group, and the expressions of Th1 cell‐associated chemokines CXCL10 and CXCL12 at each time point was significantly higher than the blank control group (P < .05). Imiquimod can be used to regulate the expression of Th1 and Th2 cell‐associated chemokines to control scar hyperplasia. [ABSTRACT FROM AUTHOR]

Quantifying how tides evolve with coupling between future sea level rise (SLR) and different coastline configurations is imperative for proposing appropriate coastal defense strategies. By using numerical models, we investigated tidal changes and determined a realistic trend of SLR on the Jiangsu coastal area and adjacent sea on the Yellow Sea shelf. A notable decrease in tidal range occurs in the northern shelf, and the tide increases mainly in the southern shelf. Tidal changes are of both signs, while the increase in sea level is unidirectional. Thus, the SLR effect on tide is not additive in all locations. We also explored the nonlinearity and spatial similarity in tidal range in response to the SLR considering uniform SLR scenarios with multiple levels and allowing inundation of the natural coastline. The patterns of change in tide evolution on the study domain remain linear until the SLR exceeds 2.0 m. Simulations and comparisons are further conducted between the responses of hardened and natural shoreline configurations to SLR. Hardened shoreline introduces both local and remote spatial variability in tidal responses. On the regional scale, SLR induces a shift in the tidal system in the offshore region, which controls the net energy flux into the embayment upon the coast. On the local scale, tidal dynamics are mainly a competition between net energy flux and tidal dissipation and are plausibly influenced by tidal reflection, which depends on whether a basin is tidally reflective. Plain Language Summary: China has experienced rapid economic growth and irreversible pressures from sea level rise (SLR) in the eastern coastal region. To provide future coastal defense strategies, we conduct multiple experiments to simulate how tides evolve with future SLR scenarios as well as how tides respond to different coastline configurations. We found that the future SLR can adjust the entire tidal system and control how much tidal energy flows into the local area from the deep ocean. Whether to build up or maintain a seawall for coastal defense depends on local conditions. By preserving the natural coast and removing the impermeable seawall from the radial sand ridges of China, tidal waves become more progressive on the shoals. Key Points: Tidal change remains linear under a 2.0‐m sea level rise within which a large spatial similarity was achieved on the Yellow Sea shelfDisplacement in the amphidromic point on the northern Yellow Sea shelf dominates the tidal range evolution for the Jiangsu coastal areaThe seawall of Jiangsu with SLR enlarges the tidal range where the tide is reflective but functions opposite where the tide is parallel to the coast [ABSTRACT FROM AUTHOR]

The purpose of this work is to develop dual drug-loaded poly (lactic-co-glycolic acid) (PLGA) fiber-microsphere composite scaffolds with desired morphologies and dual drug loading properties, and to investigate the release kinetics of the dual drugs, both hydrophobic and hydrophilic, from the composite scaffolds. In this study, simvastatin (SIM) and bovine serum albumin (BSA) were used as model drugs, which were incorporated into the composite scaffolds by performing electrospinning and emulsion electrospraying simultaneously. The optimum condition for electrospraying (solution concentration: 0.06 g/mL; applied voltage: 15 kV; and flow rate: 0.6 mL/h) has been obtained to prepare PLGA microspheres. The release rate of SIM and BSA from the composite scaffolds fit the first order kinetics and the Higuchi model, respectively. The results indicated that fiber-microsphere composite scaffolds had the ability to load two types of drug, suggesting the scaffolds have great potential in the field of tissue engineering and combined therapies. [ABSTRACT FROM AUTHOR]

The ZrB2-SiC-graphite composite is one of the most promising ceramics, which show significant potential in manufacturing parts served in ultra-high temperature. Micro-electrical discharge machining (micro-EDM) is an effective method in machining this conductive hard ceramic. However, the recast layer characterized by craters and micro-cracks is formed on the machined surface, resulting in poor surface quality. In this paper, micro-EDM and micro-ultrasonic machining (micro-USM) combined milling is proposed for manufacturing 3D micro-cavities in the ZrB2-SiC-graphite composite. The micro-cavity is firstly machined by micro-EDM milling, followed by micro-USM finish milling to remove the recast layer in the same system without changing the micro-tool. The machining performances are investigated with consideration of the surface topography and finishing depth. It is found that the more recast layer is removed when a higher ultrasonic amplitude, larger abrasive grain size, and lower tool feedrate are employed. Based on the preliminary experiments, the proper machining parameters are obtained and applied to the fabrication of micro-cavities. The machining results show that the surface quality is improved with the low surface roughness and absence of defect layer. Meanwhile, the high machining accuracy in the depth direction and processing efficiency are achieved. It is verified that the micro-EDM and micro-USM combined milling process is feasible for fabricating 3D micro-cavities in the ZrB2-SiC-graphite composite. [ABSTRACT FROM AUTHOR]

Ni-Al2O3 functionally graded materials (FGMs) have become important for high-temperature applications due to a continuous change in graded layers. However, the manufacturing process of Ni-Al2O3 FGMs with the traditional pulse power is a long process because the pulse power cannot real-timely adjust machining parameters to adapt the change of graded layers. This paper designed a real-time monitoring module and a parameter adjustment module, which can identify different graded layers and actively adjust machining parameters to adapt the change of graded layers. By means of the monitoring module, four major discharge states, normal, arc, insufficiency, and long pulse discharge state have been discriminated real-timely. The 70% Ni/30%Al2O3 layer and 30% Ni/70%Al2O3 layer have been distinguished based on the quantitative analysis of insufficiency and long pulse discharge waveforms. Multi-layers of Ni-Al2O3 FGMs are machined to validate the machining performance of the parameter adjustment module. Experiment results demonstrate that by adjusting the open voltage, the machining efficiency of 30% Ni/70%Al2O3 layer has been increased by six times, resulting in more time-efficient EDM process of Ni-Al2O3 FGMs. [ABSTRACT FROM AUTHOR]

In this paper, the CESE‐HLL three‐dimensional magnetohydrodynamic solar wind model is first modified to be able to work in a corona‐heliosphere integrated approach and then used to simulate the evolution of solar wind from the solar surface to the Earth's orbit during year 2008. Here high‐cadence photospheric magnetic field data are used to drive the model at the solar surface via the projected normal characteristic boundary equations. The simulated results are analyzed and quantitatively evaluated by comparing the simulated results with solar and interplanetary observations. The analyses demonstrate that our model reproduces the main pattern and the evolutionary feature of large‐scale coronal structures. The simulated results show that the height of the pseudostreamer X point is positively correlated with the distance of the coronal holes connected by the pseudostreamer. During year 2008, the helmet streamer belt is found to have a net southward displacement from the equator while the pseudostreamer belts are biased to the Northern Hemisphere. Both helmet streamer belt and pseudostreamer belts exhibit a general trend of becoming more concentrated along the equator throughout 2008. The evaluation of the simulated results at the L1 point shows that the general structures can be generated by the model, and that speed is the best among the solar wind parameters reproduced. However, the temperature of the fast solar wind and the magnitude of the interplanetary magnetic field are underestimated. The success rate of prediction and arrival time error are also calculated for magnetic field polarity reversals and stream interaction regions. Key Points: Magnetic field data‐driven simulation of the ambient solar wind is carried out for the whole of year 2008Analysis of the solar wind evolution is focused on helmet streamer and pseudostreamer global structureSimulation results are evaluated quantitatively by comparison with in situ measurements [ABSTRACT FROM AUTHOR]